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Altered circadian hemodynamic and renal function in cirrhosis.

ABSTRACT: Given that alterations in systemic hemodynamics have a profound influence on renal function in patients with cirrhosis, it is surprising that circadian variations in blood pressure (BP) and renal electrolyte excretion have scarcely been studied. Our aims were to define the relationship of 24-h ambulatory BP changes with renal tubular function and to determine the influence of endotoxemia on BP and urinary parameters.Forty healthy controls served as a comparator to 20 cirrhotic patients. They underwent 24-h ambulatory BP monitoring and 24-h urine collection.Subjects with cirrhosis demonstrated significant diurnal variations in urinary excretion of sodium (57.7 µmol/min day versus 87 µmol/min night) and creatinine (826 µg/min day versus 1202 µg/min night). Increasing severity of cirrhosis was associated with a progressive reduction in ambulatory awake systolic (P-trend = 0.015), diastolic (P-trend < 0.001) and mean BP (P-trend < 0.001). In patients with cirrhosis, the magnitude of change in BP from awake to sleep state was blunted for systolic BP (5% reduction, P = 0.039) and pulse rate (2% reduction, P < 0.001). The amplitude of variation in pulse rate was blunted with increasing severity of cirrhosis (controls 6.5, Child-Pugh Class A 5.3, Child B 3.4, Child C 1.2, P = 0.03) and the acrophase was right-shifted with increasing severity of cirrhosis. Compared with sleep state, during the awake state, endotoxin was associated with less sodium excretion and a lower systolic BP. Compared with the awake state, endotoxin was associated with a higher sleeping pulse rate (P < 0.001).Patients with cirrhosis have altered diurnal profiles in renal tubular function and blood pressure that appear to be related to endotoxemia. Determining whether endotoxemia is causally related to these perturbations will require interventional studies.

SUBMITTER: Liangpunsakul S

PROVIDER: S-EPMC5837480 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Altered circadian hemodynamic and renal function in cirrhosis.

Liangpunsakul Suthat S Agarwal Rajiv R

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20170201 2

<h4>Background</h4>Given that alterations in systemic hemodynamics have a profound influence on renal function in patients with cirrhosis, it is surprising that circadian variations in blood pressure (BP) and renal electrolyte excretion have scarcely been studied. Our aims were to define the relationship of 24-h ambulatory BP changes with renal tubular function and to determine the influence of endotoxemia on BP and urinary parameters.<h4>Methods</h4>Forty healthy controls served as a comparator ...[more]

PMID: 28186574

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Project description:RATIONALE & OBJECTIVE:The renin-angiotensin-aldosterone system (RAAS) is associated with renal and cardiovascular disease in diabetes. Unfortunately, early RAAS blockade in patients with type 1 diabetes mellitus (T1DM) does not prevent the development of complications. We sought to examine the role of hyperfiltration and RAAS activation across a wide range of T1DM duration to better understand renal hemodynamic status in patients with T1DM. STUDY DESIGN:Post hoc analysis of blood samples. SETTING & PARTICIPANTS:148 Canadian patients with T1DM: 28 adolescents (aged 16.2±2.0 years), 54 young adults (25.4±5.6 years), and 66 older adults (65.7±7.5 years) studied in a clinical investigation unit. EXPOSURE:Angiotensin II infusion (1ng/kg/min; a measure of RAAS activation) during a euglycemic clamp. OUTCOMES:Glomerular filtration rate measured using inulin clearance, effective renal plasma flow measured using para-aminohippurate, afferent (RA) and efferent (RE) arteriolar resistances, and glomerular hydrostatic pressure estimated using the Gomez equations. RESULTS:In a stepwise fashion, glomerular filtration rate, effective renal plasma flow, and glomerular hydrostatic pressure were higher, while renal vascular resistance and RA were lower in adolescents versus young adults versus older adults. RE was similar in adolescents versus young adults but was higher in older adults. Angiotensin II resulted in blunted renal hemodynamic responses in older adults (renal vascular resistance increase of 3.3% ± 1.6% vs 4.9% ± 1.9% in adolescents; P<0.001), suggesting a state of enhanced RAAS activation. LIMITATIONS:Homogeneous study participants limit the generalizability of findings to other populations. Studying older adult participants with T1DM may be associated with a survivorship bias. CONCLUSIONS:A state of relatively low RAAS activity and predominant afferent dilation rather than efferent constriction characterize early adolescents and young adults with T1DM. This state of endogenous RAAS inactivity in early T1DM may explain why pharmacologic blockade of this neurohormonal system is often ineffective in reducing kidney disease progression in this setting. Older adults with long-standing T1DM who have predominant afferent constriction and RAAS activation may experience renoprotection from therapies that target the afferent arteriole. Further work is required to understand the potential role of non-RAAS pharmacologic agents that target RA in patients with early and long-standing T1DM.

Project description:Liver cirrhosis (LC) is the final usual outcome of liver damage induced by various chronic liver diseases. Because of asymptomatic nature of LC, it is usually diagnosed at late and advanced stages, and patients are easy to miss the best timing for treatment. Thus, the early detection of LC is needed. In the prospective Korean Cancer Prevention Study-II (K-II), we aimed to identify valuable biomarkers for LC using metabolomics to distinguish subjects with incident LC (LC group) from subjects free from LC (control group) during a mean 7-year follow-up period. Metabolic alterations were investigated using baseline serum specimens acquired from 94 subjects with incident LC and 180 age- and sex-matched LC-free subjects via ultra-performance liquid chromatography (UPLC)-linear-trap quardrupole (LTQ)-Orbitrap mass spectrometry (MS). As a result of the metabolic analysis, 46 metabolites were identified. Among them, 11 and 18 metabolite level showed a significant increase and decrease, respectively, in the LC group compared to the control group. Nine metabolic pathways, including glyoxylate and dicarboxylate metabolism, amino acid metabolism, fatty acid metabolism, linoleic acid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism, were significantly different between the two groups. Logistic regression demonstrated that the LC emergence was independently affected by serum levels of myristic acid, palmitic acid, linoleic acid, eicosapentaenoic acid (EPA), lysophosphatidic acid (LPA) (18:1), glycolic acid, lysophosphatidylcholine (lysoPC) (22:6), and succinylacetone (R 2 = 0.837, P < 0.001). This prospective study revealed that dysregulation of various metabolism had the clinical relevance on the LC development. Moreover, myristic acid, palmitic acid, linoleic acid, EPA, LPA (18:1), glycolic acid, lysoPC (22:6), and succinylacetone were emerged as independent variables influencing the incidence of LC. The results support that the early biomarkers found in this study may useful for predicting and remedying the risk of LC.

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Altered circadian hemodynamic and renal function in cirrhosis.

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Altered circadian hemodynamic and renal function in cirrhosis.

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